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- Title
Co-targeting WIP1 and PARP induces synthetic lethality in hepatocellular carcinoma.
- Authors
Chen, Miaoqin; Wang, Weikai; Hu, Shiman; Tong, Yifan; Li, Yiling; Wei, Qi; Yu, Lei; Zhu, Liyuan; Zhu, Yiran; Liu, Leiming; Ju, Zhenyu; Wang, Xian; Jin, Hongchuan; Feng, Lifeng
- Abstract
Background: Hepatocellular carcinoma (HCC) is one of the most fatal cancers. Due to limited strategies for effective treatments, patients with advanced HCC have a very poor prognosis. This study aims to identify new insights in HCC to develop novel strategies for HCC management. Methods: The role of WIP1 (wild type p53 induced protein phosphatase1) in HCC was analyzed in HCC cells, xenograft model, DEN (Diethylnitrosamine) induced mice liver cancer model with WIP1 knockout mice, and TCGA database. DNA damage was evaluated by Gene Set Enrichment Analysis, western blotting, comet assay, and Immunofluorescence. Results: High expression of WIP1 is associated with the poor prognosis of patients with HCC. Genetically and chemically suppression of WIP1 drastically reduced HCC cell proliferation. Besides, WIP1 knockout retarded DEN induced mice hepato-carcinogenesis. Mechanically, WIP1 inhibition induced DNA damage by increasing H2AX phosphorylation (γH2AX). Therefore, suppression of WIP1 and PARP induced synthetic lethality in HCC in vitro and in vivo by augmenting DNA damage. Conclusion: WIP1 plays an oncogenic effect in HCC development, and targeting WIP1-dependent DNA damage repair alone or in combination with PARP inhibition might be a reasonable strategy for HCC management. 9j8VpB_Dcn3XrcuZcRTvAQ Video abstract
- Subjects
HEPATOCELLULAR carcinoma; POLY(ADP-ribose) polymerase; DNA damage; DNA repair; P53 protein; LIVER cancer
- Publication
Cell Communication & Signaling, 2022, Vol 20, Issue 1, p1
- ISSN
1478-811X
- Publication type
Article
- DOI
10.1186/s12964-022-00850-2